Aerial dissemination of Clostridium difficile spores

Background: Clostridium difficile-associated diarrhoea (CDAD) is a frequently occurring healthcare-associated infection, which is responsible for significant morbidity and mortality amongst elderly patients in healthcare facilities. Environmental contamination is known to play an important contributory role in the spread of CDAD and it is suspected that contamination might be occurring as a result of aerial dissemination of C. difficile spores. However previous studies have failed to isolate C. difficile from air in hospitals. In an attempt to clarify this issue we undertook a short controlled pilot study in an elderly care ward with the aim of culturing C. difficile from the air. Methods: In a survey undertaken during February (two days) 2006 and March (two days) 2007, air samples were collected using a portable cyclone sampler and surface samples collected using contact plates in a UK hospital. Sampling took place in a six bedded elderly care bay (Study) during February 2006 and in March 2007 both the study bay and a four bedded orthopaedic bay (Control). Particulate material from the air was collected in Ringer's solution, alcohol shocked and plated out in triplicate onto Brazier's CCEY agar without egg yolk, but supplemented with 5 mg/L of lysozyme. After incubation, the identity of isolates was confirmed by standard techniques. Ribotyping and REP-PCR fingerprinting were used to further characterise isolates. Results: On both days in February 2006, C. difficile was cultured from the air with 23 samples yielding the bacterium (mean counts 53 – 426 cfu/m3 of air). One representative isolate from each of these was characterized further. Of the 23 isolates, 22 were ribotype 001 and were indistinguishable on REP-PCR typing. C. difficile was not cultured from the air or surfaces of either hospital bay during the two days in March 2007. Conclusion: This pilot study produced clear evidence of sporadic aerial dissemination of spores of a clone of C. difficile, a finding which may help to explain why CDAD is so persistent within hospitals and difficult to eradicate. Although preliminary, the findings reinforce concerns that current C. difficile control measures may be inadequate and suggest that improved ward ventilation may help to reduce the spread of CDAD in healthcare facilities

Variation in Formulary Management Practices Within the Department of Veterans Affairs Health Care System

BackgroundAll Department of Veterans Affairs Medical Centers (VAMCs) operate under a single national drug formulary, yet substantial variation in prescribing and spending exists across facilities. Local management of the national formulary may differ across VAMCs and may be one cause of this variation.ObjectiveTo characterize variation in the management of nonformulary medication requests and pharmacy and therapeutics (P&T) committee member perceptions of the formulary environment at VAMCs nationwide.MethodsWe performed an online survey of the chief of pharmacy and an additional staff pharmacist and physician on the P&T committee at all VAMCs. Respondents were asked questions regarding criteria for use for nonformulary medications, specific procedures for ordering nonformulary medications in general and specific lipid-lowering and diabetes agents, the appeals process, and the formulary environment at their VAMCs. We compared responses across facilities and between chiefs of pharmacy, pharmacists, and physicians.ResultsA total of 212 chief pharmacists (n = 80), staff pharmacists (n = 78), and physicians (n = 54) responded, for an overall response rate of 49%. In total, 107/143 (75%) different VAMCs were represented. The majority of VAMCs reported adhering to national criteria for use, with 38 (36%) being very adherent and 69 (65%) being mostly adherent. There was substantial variation between VAMCs regarding how nonformulary drugs were ordered, evaluated, and appealed. The nonformulary lipid-lowering drugs ezetimibe, rosuvastatin, and atorvastatin were viewable to providers in the order entry screen at 67 (63%), 67 (63%), and 64 (60%) VAMCs, respectively. The nonformulary diabetes medication pioglitazone was only viewable at 58 (55%) VAMCs. In the remaining VAMCs, providers could not order these nonformulary drugs through the normal order-entry process. For questions about the formulary environment, physician respondent perceptions differed from those of staff pharmacists and chief pharmacists. Compared with pharmacy chiefs and staff pharmacists, physicians were less likely to agree that providers at their VAMC prescribed too many nonformulary medications (47% and 44% vs. 12%, P < 0.001), more likely to agree that providers must jump through too many hoops to prescribe nonformulary medication (5% and 3% vs. 25%, P < 0.001), and more likely to agree that providers make an effort to convert new patients from nonformulary to formulary lipid-lowering (65% and 73% vs. 94%, P <0.02) and diabetic medications (49% and 50% vs. 88%, P < 0.001).ConclusionsAlthough the Department of Veterans Affairs (VA) operates under a single national formulary, we found significant differences among VAMCs regarding their management of nonformulary medication requests. We also found differences among formulary leaders regarding their perception of the environment in which their VAMC's formulary is managed. These findings have important implications not just for VA, but for any organization that develops, implements, and manages drug formularies across multiple facilities

Do Blood Tests Cause Anemia in Hospitalized Patients?: The Effect of Diagnostic Phlebotomy on Hemoglobin and Hematocrit Levels

OBJECTIVE: To determine whether phlebotomy contributes to changes in hemoglobin and hematocrit levels in hospitalized general internal medicine patients. DESIGN: Retrospective cohort study. SETTING: General internal medicine inpatient service at a tertiary care hospital. PARTICIPANTS: All adult patients discharged from the Toronto General Hospital's internal medicine service between January 1 and June 30, 2001. A total of 989 hospitalizations were reviewed and 404 hospitalizations were included in our analysis. MEASUREMENTS AND MAIN RESULTS: Mean (SD) hemoglobin and hematocrit changes during hospitalization were 7.9 (12.6) g/L (P<.0001) and 2.1% (3.8%) (P<.0001), respectively. The mean (SD) volume of phlebotomy during hospital stay was 74.6 (52.1) mL. On univariate analysis, changes in hemoglobin and hematocrit were predicted by the volume of phlebotomy, length of hospital stay, admission hemoglobin/hematocrit value, age, Charlson comorbidity index, and admission intravascular volume status. The volume of phlebotomy remained a strong predictor of drop in hemoglobin and hematocrit after adjusting for other predictors using multivariate analysis (P<.0001). On average, every 100 mL of phlebotomy was associated with a decrease in hemoglobin and hematocrit of 7.0 g/L and 1.9%, respectively. CONCLUSIONS: Phlebotomy is highly associated with changes in hemoglobin and hematocrit levels for patients admitted to an internal medicine service and can contribute to anemia. This anemia, in turn, may have significant consequences, especially for patients with cardiorespiratory diseases. Knowing the expected changes in hemoglobin and hematocrit due to diagnostic phlebotomy will help guide when to investigate anemia in hospitalized patients

Inhibition of Hazara nairovirus replication by small interfering RNAs and their combination with ribavirin

<p>Abstract</p> <p>Background</p> <p>The genus <it>Nairovirus </it>in the family <it>Bunyaviridae </it>contains 34 tick-borne viruses classified into seven serogroups. Hazara virus (HAZV) belongs to the Crimean-Congo hemorrhagic fever (CCHF) serogroup that also includes CCHF virus (CCHFV) a major pathogen for humans. HAZV is an interesting model to study CCHFV due to a close serological and phylogenetical relationship and a classification which allows handling in a BSL2 laboratory. Nairoviruses are characterized by a tripartite negative-sense single stranded RNA genome (named L, M and S segments) that encode the RNA polymerase, the Gn-Gc glycoproteins and the nucleoprotein (NP), respectively. Currently, there are neither vaccines nor effective therapies for the treatment of any bunyavirus infection in humans. In this study we report, for the first time, the use of RNA interference (RNAi) as an approach to inhibit nairovirus replication.</p> <p>Results</p> <p>Chemically synthesized siRNAs were designed to target the mRNA produced by the three genomic segments. We first demonstrated that the siRNAs targeting the NP mRNA displayed a stronger antiviral effect than those complementary to the L and M transcripts in A549 cells. We further characterized the two most efficient siRNAs showing, that the induced inhibition is specific and associated with a decrease in NP synthesis during HAZV infection. Furthermore, both siRNAs depicted an antiviral activity when used before and after HAZV infection. We next showed that HAZV was sensitive to ribavirin which is also known to inhibit CCHFV. Finally, we demonstrated the additive or synergistic antiviral effect of siRNAs used in combination with ribavirin.</p> <p>Conclusions</p> <p>Our study highlights the interest of using RNAi (alone or in combination with ribavirin) to treat nairovirus infection. This approach has to be considered for the development of future antiviral compounds targeting CCHFV, the most pathogenic nairovirus.</p